Determination of pyrrole–imidazole polyamide in rat plasma by liquid chromatography–tandem mass spectrometry
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- 作者：Takashi Nagashima ; Takahiko Aoyama ; Akiko Fukasawa ; Satoshi Watabe ; Noboru Fukuda ; Takahiro Ueno ; Hiroshi Sugiyama ; Hiroki Nagase ; Yoshiaki Matsumoto
- 关键词：Pyrrole– ; imidazole polyamide ; Solid-phase extraction ; LC– ; MS/MS ; Plasma ; Rat
- 刊名：Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences
- 出版年：2009
- 出版时间：15 April 2009
- 年：2009
- 卷：877
- 期：11-12
- 页码：1070-1076
- 全文大小：301 K
文摘
Pyrrole (Py)–imidazole (Im) polyamides synthesized by combining N-methylpyrrole and N-methylimidazole amino acids have been identified as novel candidates for gene therapy. In this study, a sensitive method using liquid chromatography–tandem mass spectrometry (LC–MS/MS) with an electrospray ionization (ESI) source was developed and validated for the determination and quantification of Py–Im polyamide in rat plasma. Py–Im polyamide was extracted from rat plasma by solid-phase extraction (SPE) using a Waters Oasis® HLB cartridge. Separation was achieved on an ACQUITY UPLC HSS T3 (1.8 μm, 2.1 × 50 mm) column by gradient elution using acetonitrile:distilled water:acetic acid (5:95:0.1, v/v/v) and acetonitrile:distilled water:acetic acid (95:5:0.1, v/v/v). The method was validated over the range of 10–1000 ng/mL and the lower limit of quantification (LLOQ) was 10 ng/mL. This method was successfully applied to the investigation of the pharmacokinetics of Py–Im polyamide after intravenous administration.